Figure 2.
Distinct ephrin reverse signaling in presynaptic structure. Upon encountering Eph molecules expressed on the surface of target cells, ephrin-As interact with neurotrophin receptor TrkB and P75 NTR to regulate axon growth/attraction and retraction/pruning. Ephrin-A molecules also recruit ADAM10 to cleave the attachment of ephrin-As to terminate the signals. In contrast to ephrin-A molecules, ephrin-B molecules become clustered and tyrosine phosphorylated upon axon-cell contact. This results in Grb4 binding to ephrin-B3 via its SH2 domain and recruitment of both Dock180 and PAK via its second SH3 domain to increase Rac-GTP levels and downstream of active Rac for axon retraction/pruning. In addition, the PDZ binding motif in the C-terminus of ephrin-B is able to bind syntenin to induce presynaptic development.
